CHAPTER 28 Vascular Diseases 28 28.1 Physiology of the Cerebral Circulation 542 28.8.3 Neuropathology 566 28.2 Anatomy of Cerebral Vessels 543 28.9 Spontaneous Intracerebral Hemorrhage 569 28.9.1 Incidence 569 28.3 Pathology of Cerebral Arteries 543 28.9.2 Clinical Features 569 28.3.1 Cerebral Atherosclerosis 543 28.9.3 Neuropathology 571 28.3.2 Brain Calcinosis 545 28.9.3.1 Causes of Spontaneous 28.3.3 Cerebral Thromboembolism 546 Intracerebral Hemorrhage 572 28.3.4 Hypertensive Angiopathy 546 28.3.5 Lacunar Infarcts 548 28.10 Vascular Diseases of the Spinal Cord 573 28.3.6 Amyloid Angiopathy 548 28.10.1 Anatomy of the Spinal Vessels 573 28.3.7 Cystic Medial Necrosis 549 28.10.2 Pathology of the Spinal Vessels 573 28.3.8 Aneurysms 549 28.3.8.1 Saccular (Fusiform) Aneurysm 550 28.11 Forensic Aspects of Stroke 574 28.3.8.2 Dissecting Aneurysm 552 28.3.8.3 Infectious (Mycotic) Aneurysm 553 Bibliography 574 28.3.8.4 Mechanically Induced Aneurysm 553 28.3.9 Inflammatory Vessel Disease (Vasculitis) 553 References 574 28.3.9.1 Non-Infectious Primary CNS Vasculitis 553 28.3.9.2 Infectious Vascular Diseases 554 Acute and unexpected death can result from the 28.4 Pathology of Cerebral Veins 555 spontaneous (i.e. not induced by external vio- 28.4.1 Cerebral Venous Thrombosis 555 lence) fatal cerebrovascular disturbances known as “stroke.” Sacco (1994) defines stroke as an “abrupt 28.5 Vascular Malformations 557 onset of focal or global neurologic symptoms caused 28.5.1 Cavernous Angioma 557 by ischemia or hemorrhage.” Symptoms that are only 28.5.2 Capillary Angioma 557 transitory or that “resolve within 24 hours” (Kalimo 28.5.3 Venous Angioma 557 et al. 2002) are characteristic of a “transient ischemic 28.5.4 Arteriovenous Malformation 558 attack” (TIA). 28.5.5 Von Hippel−Lindau Hemangioblastoma 558 Both stroke and TIA have pathogenetic back- grounds including a variety of diseases affecting 28.6 Tumor-Induced Stroke 558 global circulation as well as local arteries and veins 28.6.1 Thrombosis and Embolism 559 (for review see Zülch and Hossmann 1988). Their se- 28.6.2 Tumor Vessels and Hemorrhage 559 quelae are attributable to the reduction of cerebral blood flow or rupture of vessels, i.e.,: 28.7 Extracerebral Causes of Stroke 561 ▬ Cerebral infarct is a consequence of reduced or 28.7.1 Coagulopathy, Hemostatic Disorder, stopped cerebral blood flow: according to Futrell Cerebral Thrombosis 561 (1998) this is referred to as: 28.7.2 Cerebral Embolism 561 − “Embolic” (definite only if a source of embo- 28.7.3 Circulatory Disturbance 561 lism was proven, suspected if cerebral infarcts 28.7.4 Illegal Drugs 564 were bilateral). − “Hemodynamic” (if there was a tight carotid 28.8 Ischemic Stroke: Infarction 564 stenosis thought to produce stroke by de- 28.8.1 Classification of Cerebral Ischemia 565 creased flow past the stenosis or if there was 28.8.2 Clinical Features decreased cardiac output or decreased blood of Transient and Permanent Focal Ischemia 565 pressure). 542 PART VI: Clinical Neuropathology − “Lacunar” (implying “hypertensive small- apy, which is suggested to be of benefit to patients vessel disease”) if the stroke was small and with acute ischemic infarct (Larrue et al. 1997). On deep, even though the patient may not have a the other hand a spontaneous hemorrhage may oc- history of hypertension. cur that can be explained by a parallel loss of three − “Thrombotic” (if none of the other three basal lamina components, which contribute to a loss “mechanisms” could be demonstrated), which of microvascular integrity (Hamann et al. 1995). was thought to be the major mechanism for The vascular diseases associated with stroke are stroke. described below. In most cases stroke is followed by ▬ Cerebral hemorrhage is usually caused by the a slow disease course, sometimes however by acute, rupture of an arterial or venous wall, less often unexpected death. The morphological changes in by arterial or venous occlusion. the brain parenchyma after vessel occlusion or rupture are also described, i.e., the cerebral infarct The effect of stroke is damage of brain tissue (in- (pp. 564 ff)and the cerebral hemorrhage (pp. 569 ff). farct) or impairment of CNS function secondary to For information on the non-natural causes of stroke an intracranial space-occupying hemorrhage and/or and/or hemorrhage the reader is referred to Parts II edema with consequent displacement of brain pa- and V (for ischemic and hypoxic changes of the brain, renchyma. see Part III). The following description is based pri- The clinical symptoms of stroke are dependent marily on Kalimo et al. (2002). on: 1. The extent of the rupture in the vascular wall and whether an artery or vein is involved 2. The size of the occluded artery 28.1 3. The age of the patient Physiology 4. The suddenness of the event of the Cerebral Circulation 5. The site of the affected brain parenchyma 6. How early therapeutic measures are initiated The physiology of the cerebral circulation is de- scribed in greater detail in Part III. Only the data Strokes can be caused by a number of cerebrovascu- relevant to vascular diseases and their sequelae are lar diseases or by extracerebral disturbances (see be- discussed here. low), as shown by the epidemiological data. Stroke is Under normal conditions, the adult human brain the third leading cause of death in the industrialized receives 15−20% of the cardiac output. The average Western world (Jörgensen and Torvik 1969; Wolf blood flow to the brain as a whole is 750 ml/100 g 1990; Sacco 1994). As a major cause of long-term dis- per min (for review see Powers 1990), the gray mat- ability, it is the number one cause, representing an ter receiving approximately 80 ml/100 g per min, and economic problem of enormous proportions. The the white matter 20 ml/100 g per min. The cerebral age-adjusted annual incidence of all first-ever strokes venous pressure is usually equal to the intracranial varies between 90 and 350 per 100,000 (Terent 1993). pressure. The force driving blood to the brain is the The mortality rate of stroke depends largely on age: cerebral perfusion pressure. The pressure can change the age-specific death rates by stroke calculated from if an obstruction causes a 70% reduction in the di- the 70th year of life double after every 5 years (Mil- ameter of the major arteries to the brain (carotid and likan et al. 1987). The main risk factors for stroke are vertebral arteries) distal to the obstruction for which hypertension, diabetes mellitus, and obesity; addi- the collateral circulatory pathways are unable to tional factors include alcohol abuse, cigarette smok- compensate. Carbon dioxide is a known vasodilator ing, oral contraceptives, atrial fibrillation, etc. of cerebral blood vessels. Reduced hematocrit and he- The most common result of cerebral vessel dis- moglobin are associated with an increase in cerebral ease is cerebral ischemic infarct (60−80%), followed blood flow (for further information, see pp. 561 f). by intracerebral hemorrhages (10%), and subarach- A drop in cerebral perfusion pressure results in noid hemorrhages (5−10%) (Kalimo et al. 2002). The an automatic dilation of cerebral arterial vessels, Framingham Study found that about 400 out of a pop- thus reducing resistance and maintaining blood ulation of 5,184 persons over 26 years of age suffered flow. A rise in perfusion pressure to the cranium, in stroke, 223 of whom died. Eighty-two percent died contrast, causes cerebral arteries and arterioles to after spontaneous intracerebral hemorrhage, 46% constrict. An increase in intracranial pressure there- after subarachnoid hemorrhage (SAH), 16% after ce- fore creates a vasodilation resembling that ensuing rebral embolism, and 15% after infarction (Sacco et upon a decrease in arterial blood pressure. al. 1982; see also Bamford et al. 1990). We also have to Autoregulation is effective under normal con- draw attention to the possibility of transformation of ditions for intracranial pressures between 60 and an acute ischemic infarct into a hemorrhagic stroke. 150 mmHg. A reduction in pressure below 60 mmHg This may be the consequence of thrombolytic ther- exceeds the vasodilatory capacity of vessels, with a CHAPTER 28: Vascular Diseases 543 consequent drop in cerebral blood flow. If pressure 2002). The spinal cord has its own, separate source of exceeds 150 mmHg, the vasoconstrictive capacity blood supply. of vessels is inadequate to prevent a rise in cerebral Microscopically and functionally, intracranial blood flow that further increases intracranial pres- vessels and extracranial vessels differ only slightly: sure. intracranial vessels have walls that are thinner per Brain metabolism depends almost entirely for its unit diameter. They possess a relatively robust in- energy needs on the ability to generate high-energy ternal elastic lamina but no, or only a rudimentary, phosphate compounds via glucose oxidation. Glu- external elastic lamina. The brain lends little adven- cose consumption is normally about 30 µmol/100 g titial support. Rich anastomoses are localized in the per min, oxygen consumption about 165 µmol/100 g gray matter, end arteries and terminal venules in the per min. Approximately 90% of glucose is metabo- white matter. lized to carbon dioxide and water. The intracerebral capillaries differ functionally Cerebral metabolism affects blood flow depend- from extracerebral capillaries in being responsible ing upon cerebral activity. At rest, the brain utilizes for maintaining the blood−brain barrier. This task is only about one-tenth of the glucose and one-third accomplished mainly by the specialized endothelial of the oxygen supplied by arterial blood flow.